Acetaminophen And Codeine and Aprepitant: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 1, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Acetaminophen And Codeine
Aprepitant
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
Your pain medicine contains codeine, and aprepitant (used to prevent nausea) can slow down how your body handles it. Codeine has to be broken down by the body to work, and part of that process (an enzyme called CYP3A4) is slowed by aprepitant. This can let more codeine and its active form, morphine, build up. That could make you more drowsy or, in some cases, slow your breathing.
This concern is mostly theoretical, but because slowed breathing can be serious, it is worth watching. The good news: your care team can manage this by adjusting your dose and keeping a closer eye on you. Please don't stop either medicine on your own. Just check with your pharmacist or doctor.
Effect: Aprepitant, a moderate CYP3A4 inhibitor, may reduce CYP3A4-mediated clearance of codeine, increasing codeine and its active metabolite morphine exposure. This raises risk of increased or prolonged opioid effects, including sedation and potentially fatal respiratory depression.
- Direction: Increased opioid effect (codeine and morphine accumulation).
- Evidence: Theoretical; magnitude not quantified.
- Onset: Unspecified.
- Management: If used together, monitor for respiratory depression and sedation; consider codeine dose reduction until stable effects seen. On aprepitant discontinuation, watch for withdrawal and consider increasing codeine dose until stable.
What happens
Increased codeine and morphine exposure
Interaction Deep Dive
Concomitant use of codeine with CYP3A4 inhibitors has resulted in increased codeine and morphine concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression, particularly when an inhibitor is added after a stable dose of codeine is achieved. If concomitant use is needed, closely monitor patients for respiratory depression and sedation, and consider dose reduction of codeine until stable drug effects have been observed. If a CYP3A4 inhibitor is being discontinued, monitor patients for signs of opioid withdrawal, and consider increasing dose of codeine until stable drug effects have been observed12.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated codeine metabolism
How to manage this interaction
Both medicines can usually be used together with the right precautions. Your care team may:
- Watch you more closely for excess drowsiness or slowed breathing, especially when aprepitant is first added.
- Adjust and individualize your codeine dose, sometimes lowering it until they see how you respond.
- Re-check things when aprepitant is stopped, watching for withdrawal and adjusting the codeine dose again if needed.
Keep taking both as prescribed. Tell your pharmacist or doctor if you feel unusually sleepy, confused, or notice slow or shallow breathing, and ask them before changing anything.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Aprepitant together?
Aprepitant can raise codeine and morphine levels, so watch for extra drowsiness or slowed breathing; your care team can manage this with dose adjustments and closer monitoring, so keep taking both as prescribed and report any warning signs. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Aprepitant interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Acetaminophen And Codeine and Aprepitant interaction managed?
Both medicines can usually be used together with the right precautions. Your care team may: Watch you more closely for excess drowsiness or slowed breathing, especially when aprepitant is first added. Adjust and individualize your codeine dose, sometimes lowering it until they see how you respond. Re-check things when aprepitant is stopped, watching for withdrawal and adjusting the codeine dose ag… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Acetaminophen And Codeine or Aprepitant need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (2)
- Product Information: Codeine sulfate oral solution, codeine sulfate oral solution. Hikma Pharmaceuticals USA Inc(per FDA), Berkeley Heights, NJ, 2023. DailyMed
- Product Information: Codeine sulfate oral tablets, codeine sulfate oral tablets. Hikma Pharmaceuticals USA Inc. (per FDA), Berkeley Heights, NJ, 2023. DailyMed
Keep reading about Acetaminophen And Codeine
Keep reading about Aprepitant
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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